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A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose\u2013response curves. The shape of the dose\u2013response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose\u2013response curve remain largely unclear. Here, we show in\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    that the distinctively shallow dose\u2013response curve of the antibiotic trimethoprim is caused by a negative growth\u2010mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA\/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose\u2013response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth\u2010mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.\n                  <\/jats:p>","DOI":"10.15252\/msb.202110490","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T04:44:38Z","timestamp":1663649078000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Growth\u2010mediated negative feedback shapes quantitative antibiotic response"],"prefix":"10.1038","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8619-2223","authenticated-orcid":false,"given":"S Andreas","family":"Angermayr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-4032","authenticated-orcid":false,"given":"Tin Yau","family":"Pang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Chevereau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Mitosch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3940-1621","authenticated-orcid":false,"given":"Martin J","family":"Lercher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-476X","authenticated-orcid":false,"given":"Tobias","family":"Bollenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"BFMSB202110490_CR1","doi-asserted-by":"crossref","DOI":"10.1038\/msb4100050","volume":"2","author":"T Baba","year":"2006","unstructured":"Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006) Construction of Escherichia coli K\u201012 in\u2010frame, single\u2010gene knockout mutants: the Keio collection. 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